A wide variety of delivery systems are available for preventative or therapeutic administration of medicaments. Methods well known in the field include injection (subcutaneous, intravenous, intramuscular or intraperitoneal), delivery via a catheter, diffusion from a patch applied to the skin or a bolus implanted under the skin, intraocular delivery via liquid drops, ingestion of a pill, capsule or gelcap, and inhalation of an aerosol. Aerosol delivery systems generally rely on a mixture of the therapeutically active agent with one or more propellants and inactive ingredients to increase dispersion and stability of the active agent. Inhalation of the aerosol can be via either the nose or mouth and often is self-administered. Because of the small volume of each dosage, the propellant generally evaporates simultaneously or shortly after delivery of the active ingredient.
Fluorocarbons are fluorine substituted hydrocarbon compounds that are biocompatible. Brominated fluorocarbons and other fluorocarbons are also known to be safe, biocompatible substances when appropriately used in medical applications. In addition to their use as aerosol propellants, they have been used in medical applications as imaging agents and as blood substitutes. U.S. Pat. No. 3,975,512 to Long uses fluorocarbons, including brominated perfluorocarbons, as a contrast enhancement medium in radiological imaging.
Gases in general, including oxygen and carbon dioxide, are highly soluble in some fluorocarbons. This characteristic has permitted investigators to develop emulsified fluorocarbons as blood substitutes. For a general review of the use of fluorocarbons as blood substitutes see "Reassessment of Criteria for the Selection of Perfluorochemicals for Second-Generation Blood Substitutes: Analysis of Structure/Property Relationship" by Jean G. Riess, Artificial Organs 8:34-56, 1984.
Oxygenatable fluorocarbons act as a solvent for oxygen. They dissolve oxygen at higher tensions and release it as the partial pressure decreases; carbon dioxide is similarly stored and released. When a fluorocarbon is used intravascularly, oxygenation of the fluorocarbon occurs naturally through the lungs. However, the fluorocarbon can be oxygenated prior to use in applications such as percutaneous transluminal coronary angioplasty, stroke therapy and organ preservation.
Liquid breathing using oxygenated fluorocarbons has been demonstrated on several occasions. For example, an animal submerged in an oxygenated fluorocarbon liquid may exchange oxygen and carbon dioxide normally when the lungs fill with the fluorocarbon. Although the work of breathing is increased in total submersion experiments, the animal can derive adequate oxygen for survival by breathing the oxygenated fluorocarbon liquid.
Full liquid breathing as a therapy presents significant problems. Liquid breathing in a hospital setting requires dedicated ventilation equipment capable of handling liquids. Moreover, oxygenation of the fluorocarbon being breathed must be accomplished separately. The capital costs associated with liquid breathing are considerable. Partial liquid ventilation techniques as disclosed in related U.S. application Ser. No. 07/695,547 are a safe and convenient clinical application of liquid breathing using oxygenated fluorocarbons.
A wide variety of pulmonary conditions exist in humans that are treatable with medicaments. Some conditions result from congenital defects, either as the result of premature birth and inadequate development of the lungs or from genetic abnormalities. One of these is Respiratory Distress Syndrome (RDS) that occurs in premature infants. Other distress conditions result from trauma to the lungs induced by exposure to particulate matter, infectious agents or injury. Adult Respiratory Distress Syndrome (ARDS) results from pulmonary trauma in adults. Infectious agents (bacterial, viral and fungal) can damage lungs by local infections and treatment of such diseases is well known. Immunocompromised patients such as people suffering from Acquired Immunodeficiency Syndrome (AIDS) or people undergoing drug treatment to suppress immunological rejection of transplanted organs also have increased susceptibility to lung infections. Lung cancer also affects thousands of people throughout the world and often results in their death. These diseases reflect only some of a wide variety of medical conditions associated with pulmonary distress.